Nitrilase-catalysed desymmetrisation of 3-hydroxyglutaronitrile: preparation of a statin side-chain intermediate

…, K Holt-Tiffin, JR Knight, T Mahoney…

Index: Bergeron, Sophie; Chaplin, David A.; Edwards, John H.; Ellis, Brian S. W.; Hill, Catherine L.; Holt-Tiffin, Karen; Knight, Jonathan R.; Mahoney, Thomas; Osborne, Andrew P.; Ruecroft, Graham Organic Process Research and Development, 2006 , vol. 10, # 3 p. 661 - 665

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Citation Number: 79

Abstract

An efficient, scaleable synthesis of ethyl (R)-4-cyano-3-hydroxybutyrate, a potential intermediate in the synthesis of Atorvastatin (Lipitor), has been developed. The three-stage process starts with reaction of low-cost epichlorohydrin with cyanide to give 3- hydroxyglutaronitrile (3-HGN). The second stage utilises a nitrilase-catalysed desymmetrisation of 3-HGN. The nitrilase reaction has been optimized to work at 3 M (330 ...